We have continued our studies of the GATA family of proteins and their role in the regulation of gene expression during development; three members are required for formation of functional hematopoietic cells in transgenic mice. In work on the erythroid factor GATA-1, we have extended studies designed to define the purpose of the N- terminal zinc finger. We have shown that this finger is essential for DNA binding at a group of double GATA sites, that it can inhibit C-terminal finger binding at some sites and that its presence can cause the two fingers to act as a composite domain with DNA binding specificity distinct from the individual fingers. The conformation of the GATA-1/DNA complexes adopted in these interactions can vary widely depending on the sequence and spacing of the DNA sites. This in turn can affect the ability of the protein to function as a trans-activator and suggests that GATA-1 may serve different functions that are directed by its DNA site. GATA-1 is capable of bending DNA, of altering chromatin structure and of mediating LCR activity and our findings provide potential new mechanisms for differential gene regulation by GATA factors. We have also cloned and analyzed the gene for chicken GATA-2, a critical regulatory molecule in all hematopoietic cell development. We have discovered that the expression of the gene is controlled by two widely separated promoters, but that expression in almost all cells and tissues is primarily under control of a proximal promoter.